crossing96/oncoscreening huggingface dataset:
In vitro synergistic cytotoxicity of gemcitabine and pemetrexed and pharmacogenetic evaluation of response to gemcitabine in bladder cancer patients.	The present study was performed to investigate the capability of gemcitabine and pemetrexed to synergistically interact with respect to cytotoxicity and apoptosis in T24 and J82 bladder cancer cells, and to establish a correlation between drug activity and gene expression of selected genes in tumour samples. The interaction between gemcitabine and pemetrexed was synergistic; indeed, pemetrexed favoured gemcitabine cytotoxicity by increasing cellular population in S-phase, reducing Akt phosphorylation as well as by inducing the expression of a major gemcitabine uptake system, the human equilibrative nucleoside transporter-1 (hENT1), and the key activating enzyme deoxycytidine kinase (dCK) in both cell lines. Bladder tumour specimens showed an heterogeneous gene expression pattern and patients with higher levels of dCK and hENT1 had better response. Moreover, human nucleoside concentrative transporter-1 was detectable only in 3/12 patients, two of whom presented a complete response to gemcitabine. These data provide evidence that the chemotherapeutic activity of the combination of gemcitabine and pemetrexed is synergistic against bladder cancer cells in vitro and that the assessment of the expression of genes involved in gemcitabine uptake and activation might be a possible determinant of bladder cancer response and may represent a new tool for treatment optimization.	bladder
Early effects of combretastatin A4 phosphate assessed by anatomic and carbogen-based functional magnetic resonance imaging on rat bladder tumors implanted in nude mice.	Combretastatin A4 phosphate (CA4P) causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multiparametric magnetic resonance imaging (MRI) approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T) comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, and 24 hours after CA4P (100 mg/kg); and a fast T2w* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, and 24 hours after CA4P. The tumor fraction with increased T2w* signal intensity under carbogen (T+) was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2w* signal increase before CA4P to a decrease postCA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents.	bladder
Inverted papilloma of the urinary bladder: a molecular genetic appraisal.	Inverted papilloma of urinary bladder is an uncommon urothelial neoplasm. Its relationship to urothelial carcinoma is controversial. Little is known of the genetic abnormalities of inverted papilloma. To better understand its genetics, we analyzed 39 inverted papillomas, including 36 from men and three from women, for loss of heterozygosity (LOH). We examined four polymorphic microsatellite markers located on chromosome 9q32-33(D9S177), chromosome 9p22 (IFNA), chromosome 3p14.2 (D3S1300) and chromosome 17p13.1 (TP53), where genetic alterations occur frequently in urothelial carcinomas. Additionally, the status of inactivation of X-chromosome was examined in three female patients. The frequency of LOH in informative cases was 8% (3 of 37) for D9S177, 10% (4 of 38) for TP53, 8% (3 of 37) for IFNA and 8% (3 of 36) for D3S1300. In the analysis of X-chromosome inactivation, all three cases yielded informative results and one had nonrandom inactivation of X-chromosomes. The monoclonal origin demonstrated in the study of X-chromosome inactivation indicates the clonal process of inverted papilloma; however, the low incidence of LOH supports the view that inverted papilloma in urinary bladder is a benign neoplasm with molecular genetic abnormalities different from those of urothelial carcinoma.	bladder
Modification of alternative splicing of Bcl-x pre-mRNA in bladder cancer cells.	To modify the splicing pattern of Bcl-x and compare the effect of this approach with that of the antisense gene therapy in BIU-87 cell line of bladder cancer, by using 5'-Bcl-x AS to target downstream alternative 5'-Bcl-x splice site to shift splicing from Bcl-xL to Bcl-xS and 3'-Bcl-x AS antisense to the 3'-splice site of exon III in Bcl-x pre-mRNA to down regulation of Bcl-xL expression, the inhibitory effects on cancer cells by modification of alternative splicing and antisense gene therapy were observed and compared by microscopy, MTT Assay, RT-PCR, FACS, Western bloting and clone formation. The growth of cells BIU-87 was inhibited in a dose- and time-dependent manner. Its inhibitory effect began 12 h after the exposure, reaching a maximum value after 72h. The number of cells decreased in S phase and the number increased in G1 phase. The ability to form foci was reduced and the antisense gene therapy was approximately half as efficient as modification of alternative splicing in inducing apoptosis. It is concluded that modification of splicing pattern of Bcl-x pre-mRNA in bladder cancer cell BIU-87 is better than antisense gene therapy in terms of tumor inhibition.	bladder
Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium.	PURPOSE: To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis. RESULTS: Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). CONCLUSION: Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.	bladder
[Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer].	We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year nonrecurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88%), respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers.	bladder
Cutaneous complications of intravesical treatments for bladder cancer: granulomatous inflammation of the penis following BCG therapy and penile gangrene following mitomycin therapy.	Transitional cell carcinoma of the bladder is frequently treated with intravesical injection of immunotherapeutic (eg, BCG) or chemotherapeutic (eg, mitomycin C) agents. The aim of this study was to report cutaneous complications of intravesical therapy in 2 patients with transitional cell carcinoma of the bladder. A 69-year-old man had an ulceration at the base of the penis and papules involving the glans penis 1 month after injection of intravesical BCG. Biopsy findings showed granulomatous inflammation with foci of dermal necrosis suggestive of a BCG-related granulomatous reaction. The second patient was a 73-year-old man with penile gangrene. Erythema involving his penis and perineum had developed within 24 hours after intravesical administration of mitomycin C, which spilled onto his perineum during catheter removal. The resulting penile gangrene required penectomy 3 months after the injection. Mitomycin C patch testing showed a clear allergic contact reaction. Dermatologists should be aware of these potential cutaneous complications.	bladder
Granulocyte colony-stimulating receptor promotes beta1-integrin-mediated adhesion and invasion of bladder cancer cells.	OBJECTIVES: To determine whether granulocyte colony-stimulating factor receptor (G-CSFR) autocrine signaling promotes endothelial cell adhesion and invasion of bladder cancer cells through a beta1-integrin-mediated pathway. A significant fraction of invasive bladder carcinomas express both G-CSF and G-CSFR. Bladder carcinoma cell line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. Thus, we studied the effects of G-CSFR expression on cell adhesion and invasion in this unique model system. METHODS: Flow cytometry and adhesion assay were performed to detect expression of beta1-integrin in G-CSFR-expressing 5637 cells and adhesion of these cells to human umbilical vein endothelial cell, respectively. Furthermore, an invasion chamber assay was done with the 5637 cells. Next, we used the G-CSF-specific antibody, siRNA, and a truncated version of G-CSFR (GR19) to block G-CSFR autocrine loop in these cells. We also used a beta1-integrin-specific neutralizing antibody in the adhesion and invasion assays with the 5637 cells. RESULTS: G-CSFR-mediated increased expression (approximately threefold) of beta1-integrin is significantly abrogated by G-CSF specific antibody or siRNA in 5637 cells. GR19 also completely blocked beta1-integrin expression. G-CSFR signaling increased adhesion (approximately 2.5-fold) of 5637 cells to human umbilical vein endothelial cells, which are potently blocked by beta1-integrin-specific antibody. G-CSF/G-CSFR autocrine signaling significantly increased the invasiveness of 5637 cells (approximately 10-fold), which was reduced by either attenuating G-CSF production (G-CSF-specific antibody and siRNA) or interfering with G-CSFR signaling (GR19). Furthermore, beta1-integrin-specific antibody completely blocked G-CSFR-mediated invasion of 5637 cells. CONCLUSIONS: Autocrine G-CSF/G-CSFR signaling in bladder cancer can significantly contribute to cancer cell adhesion and invasion in a beta1-integrin-dependent manner.	bladder
Smoking and bladder cancer in Spain: effects of tobacco type, timing, environmental tobacco smoke, and gender.	We examined the effects of dose, type of tobacco, cessation, inhalation, and environmental tobacco smoke exposure on bladder cancer risk among 1,219 patients with newly diagnosed bladder cancer and 1,271 controls recruited from 18 hospitals in Spain. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between bladder cancer risk and various characteristics of cigarette smoking. Current smokers (men: OR, 7.4; 95% CI, 5.3-10.4; women: OR, 5.1; 95% CI, 1.6-16.4) and former smokers (men: OR, 3.8; 95% CI, 2.8-5.3; women: OR, 1.8; 95% CI, 0.5-7.2) had significantly increased risks of bladder cancer compared with nonsmokers. We observed a significant positive trend in risk with increasing duration and amount smoked. After adjustment for duration, risk was only 40% higher in smokers of black tobacco than that in smokers of blond tobacco (OR, 1.4; 95% CI, 0.98-2.0). Compared with risk in current smokers, a significant inverse trend in risk with increasing time since quitting smoking blond tobacco was observed (> or =20 years cessation: OR, 0.2; 95% CI, 0.1-0.9). No trend in risk with cessation of smoking black tobacco was apparent. Compared with men who inhaled into the mouth, risk increased for men who inhaled into the throat (OR, 1.7; 95% CI, 1.1-2.6) and chest (OR, 1.5; 95% CI, 1.1-2.1). Cumulative occupational exposure to environmental tobacco smoke seemed to confer increased risk among female nonsmokers but not among male nonsmokers. After eliminating the effect of cigarette smoking on bladder cancer risk in our study population, the male-to-female incidence ratio decreased from 8.2 to 1.7, suggesting that nearly the entire male excess of bladder cancer observed in Spain is explained by cigarette smoking rather than occupational/environmental exposures to other bladder carcinogens.	bladder
C-choline positron emission tomography in bladder cancer: report of four cases.	Little work has been done with positive emission tomography (PET) in bladder tumors because high urinary excretion of (18)F-FDG makes visualization of the bladder tumor difficult. (11)C-choline has recently been reported as a new tracer which lacks urinary radioactivity. We report the result of (11)C-choline PET in four patients with invasive bladder tumors. In one case, (11)C-choline PET could detect bladder tumor effectively without urinary activity and bone metastasis despite negative bone scintigraphy. On the other hand, an intense accumulation of the tracer in the bladder hampered the interpretation on PET scanning in three patients. The mechanisms of the (11)C-choline accumulation in the bladder were reported to be due to inflammatory and proliferative changes in the mucosa of the bladder from previous catheterization or other factors. Further study is necessary to prove the value of (11)C-choline PET for detecting primary bladder cancer and bone metastasis.	bladder
Superficial transitional cell carcinoma of the ureteral orifice: higher risk of developing subsequent upper urinary tract tumors.	AIM: Reports specifically addressing transitional cell carcinoma (TCC) of the ureteral orifice are scarce. This paper presents our experiences of such tumors, including the characteristics of the disease and the incidence of subsequent upper urinary tract recurrence. METHODS: This study included 572 new cases of TCC of the urinary bladder diagnosed in our institute during a period of 5 years. Thirty-one (5.4%) patients had superficial tumors involving ureteral orifices. All 31 patients underwent transurethral resection of the bladder tumors, including the involved ureteral orifices. After the surgery, patients received regular follow up with cystourethroscopy, urine cytology and periodic intravenous pyelography (IVP). Ureterorenoscopy was performed in cases of suspicious IVP or urine cytology findings. RESULTS: Thirty-one patients with superficial tumors involving the ureteral orifice were followed up for 5-8 years or until death. The pathological stage was Ta in 16 cases and T1 in 15 cases. Bladder tumor recurrence was noted in three (18.8%) of the pTa patients and in seven (46.7%) of the pT1 patients. Subsequent upper urinary tract tumors developed in four (12.9%) patients between 33 and 67 months (mean: 33.5) after the first transurethral resection. All four cases of upper tract recurrence had pT1 primary bladder tumor, which recurred for 1-3 times (mean 1.8) before upper tract recurrence. None of these patients had ureteral stenting after bladder tumor resection. Three of four patients with upper tract recurrence had single lower ureteral tumor, while the remaining one patient had multiple tumors. Patients with subsequent upper urinary tract tumors underwent nephroureterectomy and bladder cuff excision. One died of the disease; the other three cases were free of the disease after the therapy. CONCLUSIONS: Patients with primary superficial bladder transitional cell carcinoma involving the ureteral orifice have a higher risk of developing subsequent upper urinary tract tumors, particularly for pT1 primary bladder tumors. Frequent and close follow up is recommended.	bladder
Precystectomy nomogram for prediction of advanced bladder cancer stage.	OBJECTIVE: To evaluate precystectomy prediction of pT and pN stages at cystectomy. METHODS: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. RESULTS: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage. CONCLUSION: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.	bladder
The role of imaging in the surveillance of urologic malignancies.	Urologic malignancies are common, accounting for approximately 25% of all new cancer cases in the United States. Patients with urologic malignancies require long-term surveillance to detect progression or recurrence as early as possible. The urologist is faced with the task of balancing patient safety and cost-effectiveness, while finding the most practical follow-up regimen. For each urologic malignancy, this article reviews the commonly used radiologic techniques for surveillance and offers recommended follow-up schedules.	bladder
Significance of cancer involvement at the ureteral margin detected on routine frozen section analysis during radical cystectomy.	INTRODUCTION: We investigated the clinical significance of preoperatively-unsuspected ureteral involvement of cancer detected on intraoperative frozen section analysis of ureteral margins during radical cystectomy. PATIENTS AND METHODS: We performed a retrospective study of 115 patients who received radical cystectomy for locally-advanced but node-negative transitional cell carcinoma of the bladder between 1995 and 2002 by reviewing their records. RESULTS: Of 115 total patients, 5 (4.3%) demonstrated carcinoma in situ at the ureteral margin with 2 of 5 having a positive margin on final pathologic analysis. Meanwhile, only 3 of 115 total patients (2.6%) later showed upper urinary tract recurrence at a median interval of 30 months after cystectomy. And all 3 patients had intramural or juxtavesical ureter involvement of disease (p = 0.006), while not demonstrating carcinoma in situ in ureteral margins resected during cystectomy. On multivariate analysis, only the stage and grade of bladder cancer along with pathologic feature of vascular invasion were observed to be independent prognostic predictors of disease-specific survival. CONCLUSIONS: Cancer involvement of the distal ureteral margin detected through intraoperative frozen section analysis may not be a significant factor regarding upper tract recurrence and survival of patients with locally-advanced bladder cancer after radical cystectomy. Upper tract recurrence may be more prone to occur in patients with cancer involvement at the intramural or juxtavesical ureter.	bladder
[Urinary cytology. Possibilities, limitations and the future].	Even now, 60 years after the fundamental studies on oncological urinary cytology carried out by Papanicolaou and Marschall and the subsequent integration of the test they devised into the diagnostic investigations applied in the diagnosis of urothelial carcinoma, urinary cytology still maintains its place in the diagnosis of primary and recurrent tumours of the urinary tract. Newer diagnostic techniques involving urine-bound tumour markers have not so far achieved such high levels of acceptance as their method. It is possible, certainly, that a combination of these newer methods with cytological testing, or with other innovative diagnostic methods, such as photodynamic techniques, could prove very promising in the future and might overcome the limitations of urinary cytology.	bladder
Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer.	No prognostic marker for predicting recurrence in primary superficial bladder cancer has been established. The aim of this study was to investigate the expression levels of thymidine phosphorylase (TP) by enzyme-linked immunosorbent assay (ELISA) and the immunohistological localization of TP in primary superficial bladder cancer tissue to assess its association with tumor recurrence and stage progression as well as the pathological parameters of the tumor. TP expression in cancer tissues from 77 patients was measured by sandwich-type ELISA. Clinicopathological factors and the clinical prognosis were examined in relation to the expression levels of TP. To clarify the clinicopathological implication of TP localization in primary superficial bladder cancer tissue, the immunohistochemically determined TP expression was assessed for histological grades 1-3. The TP expression in primary superficial bladder cancer significantly increased with the histological grade and stage. The TP expression in patients with a shift to invasive cancer was significantly higher than in those without invasive cancer. Patients with low TP expression had a significant longer postoperative tumor-free period than those with high TP expression (P=0.011). High TP expression was an independent prognostic factor for tumor recurrence (P=0.0441). Strong immunoreactivity for TP was observed in the cytoplasms of tumor cells and vascular endothelial cells. This study suggests that elevated TP expression may be a prognostic marker for predicting recurrence in primary superficial bladder cancer, and that high TP expression may be associated with the marked proliferation of tumor cells and increased vascular endothelial cells, showing strong immunoreactivity for TP.	bladder